1. Field of the Invention
This invention relates generally to the fields of immunology and medicine and, more specifically, to the use of low dose estrogen to treat immune pathologies.
2. Background Information
The involvement of female sex hormones in immune pathologies has been proposed based on a number of clinical and experimental observations. First, a variety of autoimmune diseases, including multiple sclerosis, rheumatoid arthritis and Grave's disease, preferentially affect women, and first occur during the reproductive years. Second, during pregnancy, when levels of female sex hormones are high, clinical remissions of cell-mediated autoimmune diseases are common, with disease exacerbation often seen post-partum when sex hormone levels are low. Third, in animal models of autoimmune disease, administration of estrogen at levels equal to or greater than those found in pregnancy has been shown to suppress the clinical and histopathological symptoms of the disease. Fourth, in vitro, estrogen at the high concentrations found in pregnancy has been shown to inhibit production of inflammatory cytokines and to stimulate production of anti-inflammatory cytokines by autoantigen-specific CD4+ cells from multiple sclerosis patients. However, in the same study, low concentrations of estrogen had the opposite effect, stimulating production of inflammatory cytokines, with little or no effect on production of anti-inflammatory cytokines (Correale et al., J. Immunol. 161:3365-3374 (1998).
To explain these observations, it has been proposed that the response to estrogen is biphasic, with high levels associated with protection from autoimmune disease, and low levels associated with promotion of disease. However, because of the potential adverse effects of high levels of estrogen on the reproductive and circulatory systems, and because of the potential unwanted side effects in males, administration of high levels of estrogen is unlikely to be widely useful as a therapy.
The effect of administering low dose estrogen to an individual with an immune disease has not previously been tested, although, from the clinical and experimental observations described above, little or no beneficial effect on the course of the disease would be predicted.
There exists a need to design effective therapies that are applicable for treating a variety of immune pathologies, in both genders, with minimal side effects. The present invention satisfies this need and provides related advantages as well.